What are the treatment options for hyperemesis gravidarum (hyperemesis of pregnancy) that is refractory to ondansetron (Zofran) and intravenous (IV) hydration?

From the Guidelines

For severe hyperemesis gravidarum that doesn't respond to ondansetron (Zofran) and IV hydration, a step-up approach is recommended, starting with metoclopramide 10mg IV/PO every 6-8 hours, as it has been shown to have similar efficacy to promethazine with fewer adverse events 1. When considering treatment options, it's essential to prioritize the patient's morbidity, mortality, and quality of life. The goals of management are to prevent dehydration, correct electrolyte abnormalities, and support adequate maternal and fetal nutrition.

• Treatment is guided by the severity of symptoms and may require a multidisciplinary team approach involving obstetricians, nutritionists, psychologists, and gastroenterologists.
• Mental health care professionals can help manage anxiety, depression, and other emotional challenges associated with hyperemesis gravidarum.
• Supplementation with vitamin B6 (pyridoxine) may be suggested as a first-line treatment for mild cases, while vitamin B1 (thiamine) is given to prevent refeeding syndrome and Wernicke encephalopathy, with a recommended dosage of 100 mg daily for a minimum of 7 days, followed by a maintenance dosage of 50 mg daily until adequate oral intake is established 1. If metoclopramide is not effective, methylprednisolone 16mg IV every 8 hours for up to 3 days, followed by tapering over 2 weeks to the lowest effective dosage, can be considered as a last resort in patients with severe hyperemesis gravidarum, as it reduces the rate of rehospitalization 1.
• For some patients, a combination of doxylamine 10mg and pyridoxine 10mg (Diclegis/Bonjesta) taken 3-4 times daily may help.
• Consider enteral nutrition via nasogastric or nasoduodenal tube if oral intake remains impossible.
• Hospitalization for continuous IV fluids, electrolyte replacement, and nutritional support is often necessary, and total parenteral nutrition may be required in extreme cases. These interventions work through different antiemetic pathways, providing broader coverage than ondansetron's serotonin antagonism alone.

From the Research

Treatment Options for Hyperemesis Gravidarum

For women with hyperemesis gravidarum that is refractory to ondansetron and intravenous hydration, several treatment options can be considered:

• Corticosteroids: Although a study from 2 found that the addition of parenteral and oral corticosteroids to the treatment of women with hyperemesis gravidarum did not reduce the need for rehospitalization later in pregnancy, some uncontrolled data support a beneficial effect of corticosteroids in these women 3.
• Mirtazapine: This drug has been suggested as a useful option for women who are not adequately treated with conventional medications, due to its antiemetic, sedative, and appetite-stimulating effects 4.
• Other antiemetics: Pyridoxine and metoclopramide are considered first-line treatments for hyperemesis gravidarum, followed by prochlorperazine, prednisolone, promethazine, and ondansetron 5.
• Supportive care: Intravenous rehydration, correction of vitamin deficiency, and psychological support are essential components of management 3, 6.
• Alternative therapies: Some women may find dietary and lifestyle recommendations, ginger, acupressure, and acupuncture useful, although evidence is limited or mixed 5, 6.